Energy metabolism is important in cancer proliferation and progression, but its role in prostate cancer (PCa) remains unclear.
We explored whether single-nucleotide polymorphisms (SNPs) of genes involved in energy metabolic pathways are associated with PCa risk and prognosis, and whether antidiabetic treatment modifies any such association.
Design, setting, and participants
The PRACTICAL Consortium genotyped 397 SNPs among 3241 screened participants (including 801 PCa cases) in the Finnish Prostate Cancer Screening Trial and 1983 hospital-based PCa cases. Information on medication use was obtained from a national prescription database.
Outcome measurements and statistical analysis
Genetic risk scores were calculated in terms of SNPs associated with PCa incidence or survival at a significance level of p < 5 × 10−3. Hazard ratios for PCa and disease-specific death were calculated via Cox regression modelling. The predictive value of the genetic risk score was evaluated using receiver operating characteristic and Harrell's c-index analyses.
Results and limitations
A total of 30 SNPs were associated with PCa risk and ten SNPs with survival. The genetic risk score was consistently associated with PCa survival. The risk association was non-significantly weaker in metformin users. The genetic risk score did not improve prediction of PCa risk, but slightly improved the ability to predict PCa survival when added to conventional predictors (c-index improved from 87.4 to 87.9; p < 0.001). A limitation is that information on diabetes apart from medication use was unavailable for the study population.
SNPs of genes involved in energy metabolic pathways are associated with PCa survival. This suggests an important role of glucose metabolism in PCa progression, which could point to new avenues for prevention of PCa death.
Genetic changes in glucose and energy metabolic pathways are associated with a higher risk of high-risk prostate cancer and adverse outcomes.
Keywords: Glucose metabolism, Prostate cancer, Risk, Survival.
a School of Medicine, University of Tampere, Tampere, Finland
b Department of Urology, Tampere University Hospital, Tampere, Finland
c Institute of Biosciences and Medical Technology / BioMediTech and Fimlab Laboratories, University of Tampere, Tampere, Finland
d Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
e Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland
f Institute of Biomedicine, Medical Biochemistry and Genetics, University of Turku, Turku, Finland
g School of Health Sciences, University of Tampere, Tampere, Finland
Corresponding author. School of Medicine, Building M, Room 313, University of Tampere, PL 2000, 33521 Tampere, Finland. Tel. +358 3 31165015; Fax: +358 3 31164358.
Members of the PRACTICAL Consortium are listed in Supplementary File 1.
© 2015 European Association of Urology, Published by Elsevier B.V.